Development of SP-A Derived Peptidomimetics for the Treatment of Asthma - Phase II

哮喘的当前治疗方法，同时通过专注于呼吸道来减少部分患者的病情恶化 炎症，不要消灭它们。哮喘加重是发病率和 哮喘会导致死亡，因为哮喘会导致呼吸道损伤、肺功能下降和死亡。中国的情况恶化 更严重的哮喘患者尤其令人担忧，因为医疗费用和生产力下降是 美国每年的医疗保健支出为210亿美元。目前还没有先天免疫调节剂来治疗 哮喘的治疗。因此，迫切需要开发新的治疗方法，用于 治疗包括哮喘在内的炎症性肺部疾病。我们已经发现了小分子 模拟内源性肺蛋白-表面活性蛋白A(SP-A)在减少呼吸道中的作用 与哮喘相关的收缩，会引起症状和加重。SP-A是一种天然的 肺中衬里液体的成分，是抵御吸入侮辱的第一道防线 病原体。许多哮喘患者要么SP-A水平非常低，要么由于 哮喘肺的炎性环境。直接进入肺部的全长SP-A不是 由于它的大小和结构，它是可行的。 我们的公司，RaeSedo Inc.，成立的原则是我们可以创建自定义修改 SP-A活性区域以小肽形式递送，已得到改善 药代动力学特性和稳定性。这些SP-A衍生的多肽模拟物代表了一类新的 哮喘疗法。在第一阶段，RaeSedo Inc.和亚利桑那大学努力满足 建议的里程碑：设计、合成和优化多肽仿制药，并表征 用于识别先导化合物的特定细胞靶点的多肽模拟物的生物活性。乐世多公司的S 第二阶段提案的目标是促进气雾剂的开发、药理学和评估 我们的先导化合物(C867和C892)在两个大型动物模型中的合作毒性 与亚利桑那大学和Lovelace Biomedical合作。此第二阶段提案的总体目标是 在豚草致敏犬哮喘模型上证明其安全性和有效性。如果成功， RaeSedo Inc.将准备提交IND申请，带来一种新的哮喘类别 治疗药物提交给FDA审批。

Current treatments for asthma, while reducing exacerbations in a subset of patients by focusing on airway inflammation, do not eliminate them. Asthma exacerbations are a significant cause of morbidity and mortality in asthma as they can lead to airway injury, lung function decline and death. Exacerbations in more severe asthmatics are of particular concern, as health care costs and lost productivity account for $21 billion/year in US annual health care expenditures. There is no current innate immune modulator for the treatment of asthma. Thus, there is a critical need to develop new therapies to be used in the treatment of inflammatory lung diseases including asthma. We have discovered small molecules that mimic the effect of an endogenous lung protein, Surfactant Protein A (SP-A), in reducing airway constriction associated with asthma that causes symptoms and exacerbations. SP-A is a natural component of the lining fluid in the lungs and serves as a first line of defense against inhaled insults and pathogens. Many asthma patients have either very low levels of SP-A or damaged SP-A due to the inflammatory environment of the asthma lung. Full-length SP-A delivered directly to the lungs is not feasible due to its size and structure. Our company, RaeSedo Inc., was founded on the principle that we can create custom modifications of the active region of SP-A that are delivered in small peptidomimetic form that have improved pharmacokinetic properties and stability. These SP-A derived peptidomimetics represent a new class of asthma therapeutics. During Phase I, RaeSedo Inc. and the University of Arizona, worked to meet the milestones proposed: Design, synthesize and optimize peptidomimetics and to characterize the bioactivity of the peptidomimetics at specific cellular targets to identify lead compounds. RaeSedo Inc.’s objectives for the Phase II proposal are to advance aerosol development, pharmacology and evaluation of toxicity of our lead compounds (C867 and C892) in two large animal models through collaborations with the University of Arizona and Lovelace Biomedical. The overall goal of this phase II proposal is to demonstrate safety and efficacy in the ragweed sensitized canine model of asthma. If successful, RaeSedo Inc. will be equipped to submit an IND application bringing a new class of asthma therapeutics to the FDA for approval.